Human HCMV infection is the leading infectious cause of congenital birth defects and causes important morbidity and mortality in immunocompromised patients of all ages. Humans are the only reservoir for this infection and many unique strains circulate in the general population throughout the world. Rates of congenital HCMV infection in the U.S. range from 0.2 percent to 2.2 percent of all live births, affecting approximately 10,000 to 80,000 infants born each year. The Institute of Medicine study of vaccine objectives has therefore identified congenital HCMV prevention by vaccines as a Level I priority. The overall objective of this application is to define the epidemiology and disease burden of congenital infection caused by HCMV in a diverse, Northern California population by virologically screening 20,000 newborns from three area hospitals over a two-year period. In Specific Aim 1, screening will be done using a direct early antigen detection of fluorescent foci (DEAFF) method to identify HCMV in saliva samples of newborns. We hypothesize that incidence in white infants will be different than that for Hispanic and Asian/Pacific Islander infants born in this area. Virus isolates obtained from infected infants will be tested to determine genetic relatedness and whether specific subtypes are associated with the occurrence of symptomatic vs. asymptomatic infection of the infant. To assess disease burden, we will describe clinical features in infected infants and determine the distribution of symptomatic vs. asymptomatic presentation among demographic groups. In Specific Aim 2, we will describe the incidence, severity and timing of sensorineurat hearing loss (SNHL) over three years in infected infants, and determine whether universal newborn hearing screening identifies SNHL caused by congenital HCMV. The pattern of hearing loss will be described for the cohort, and affected infants will be offered remedial treatment. In Specific Aim 3, we will describe the HCMV-specific CD4 and CD8 T cell responses of the infected cohort over three years and determine whether there are differences in immune response pattern between symptomatically and asymptomatically infected infants, and between infants and adults. Data from this study will help to define target populations for immunization and clinically relevant immune responses for vaccine researchers.